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1.
Increased amounts of serotonin as well as histamine have been found in the blood of animals during anaphylactic shock. Certain animals, particularly those in which antihistamines do not prevent anaphylaxis, have been found to have increased quantities of serotonin in the lung tissue during anaphylactic shock.Serotonin is a chemical derived from the amino acid tryptophan, which is widely distributed. It is excreted in the urine as the metabolite 5-hydroxyindoleacetic acid. Serotonin has been found in increased amounts in the blood of patients with carcinoids. The increase of serotonin in the blood and the finding of the excretory product in the urine has become a corroborative sign of the disease. The involvement of serotonin in the production of mental disease is evidenced by the effect of serotonin antagonists, which appear to influence mental behavior.That serotonin antagonists may be of ultimate value in the treatment of allergic disease is a possibility to be considered.  相似文献   

2.
The experimental investigations have been carried out on 116 guinea pigs divided in two groups: the experimental and control group. The animals of the experimental group were sensitized with a 25% egg white suspension in 0.86% conc. of NaCl applied subcutaneously. After 21 days the same animals were exposed to the action of the same antigen in aerosol according to the method of Gerszanowicz, [16]. It has been shown, that in anaphylactic shock (acute and chronic) the damage of the lysosomal membranes in hepatocytes appeared which may be the cause of liberation among others also of acid phosphatase from the liver into the blood. Histochemically it was found a low phosphorylase and glucose-6-phosphatase activity, which was the basis of the assumption, that in anaphylactic shock we have to do with an enzymatic block--phosphorylase kinase--phosphorylase and inhibition of the enzymatic activity of glucose-6-phosphatase in the liver of guinea pigs. The comparison of the histochemical and biochemical results concerned with the amount of lipids, glycogen and nucleic acids in the liver revealed that the increasing amount of lipids is paralleled by decrease of glycogen. Among nucleic acids a growing level of ribonucleic acid was found while the level of the desoxyribonucleic acid remained stable.  相似文献   

3.
1. Rat serum levels in beta-glucuronidase and beta-galactosidase are higher than plasma levels. Rat platelets release these lysosomial enzymes during blood coagulation in vitro. 2. After anaphylactic shock, in the sensitized rat, there is no increase in beta-galactosidase and beta-glucuronidase plasma levels. The tissues of the sensitized rat do not release these enzymes during the antigen-antibody reaction. The blood platelet level is diminished after anaphylactic shock and the serum levels of the lysosomial enzymes are decreased. 3. In thrombopenic rat, anaphylactic shock is identical as in control animals. Rat platelets do not play a significant role in the anaphylactic shock.  相似文献   

4.
G E Martin  C B Bacino  N L Papp 《Peptides》1981,2(2):213-217
Methergoline, an antagonist of cerebral serotonin receptors, has been shown to significantly reduce the rise in rectal temperature (Tre) produced by the intracerebral microinjection of beta-endorphin. In this study the role of serotonin in the increase in Tre elicited by beta-endorphin was further examined using three additional serotonin antagonists. beta-Endorphin was administered twice to rats using a crossover design in which half of the animals were first pretreated with the vehicle solution and half with the antagonist. Serotonin antagonists used were: methergoline, methysergide, cinanserin and cyproheptadine. Although methergoline did cause a marked reduction in the beta-endorphin-induced rise in Tre, neither methysergide, nor cinanserin, nor cyproheptadine produced a marked reduction in the hyperthermia. Since methergoline also interacts with the dopamine receptor, the effect of a dopamine antagonist, haloperidol, on the endorphin-evoked response was also examined. Haloperidol failed to attenuate the rise in Tre. The reason for the apparent discrepancy in the action of these serotonin antagonists is unclear. Further research may reveal distinct subpopulations of serotonin receptors at which these antagonists exert differential effects.  相似文献   

5.
Serotonin, a well-known neurotransmitter in mammals, has been linked to a number of neurological and gastrointestinal disorders. One of these disorders, serotonin syndrome, is a potentially deadly condition caused by increased levels of serotonin in the extracellular space. Information on the neurochemical effects of serotonin syndrome on serotonin catabolism is lacking, particularly in relation to the enteric system of the gastrointestinal tract. Here the catabolism of serotonin is monitored in rats with pharmacologically induced serotonin syndrome, with the catabolites characterized using a specialized capillary electrophoresis system with laser-induced native fluorescence detection. Animals induced with serotonin syndrome demonstrate striking increases in the levels of serotonin and its metabolites. In the brain, levels of serotonin increased 2- to 3-fold in animals induced with serotonin syndrome. A major serotonin metabolite, 5-hydroxyindole acetic acid, increased 10- to 100-fold in experimental animals. Similar results were observed in the gastrointestinal tissues; in the small intestines, serotonin levels increased 4- to 5-fold. Concentrations of 5-hydroxyindole acetic acid increased 32- to 100-fold in the intestinal tissues of experimental animals. Serotonin sulfate showed surprisingly large increases, marking what may be the first time the compound has been reported in rat intestinal tissues.  相似文献   

6.
Ventilation is a crucial motor activity that provides organisms with an adequate circulation of respiratory gases. For animals that exist in harsh environments, an important goal is to protect ventilation under extreme conditions. Heat shock, anoxia, and cold shock are environmental stresses that have previously been shown to trigger protective responses. We used the locust to examine stress-induced thermotolerance by monitoring the ability of the central nervous system to generate ventilatory motor patterns during a subsequent heat exposure. Preparations from pre-stressed animals had an increased incidence of motor pattern recovery following heat-induced failure, however, prior stress did not alter the characteristics of the ventilatory motor pattern. During constant heat exposure at sub-lethal temperatures, we observed a protective effect of heat shock pre-treatment. Serotonin application had similar effects on motor patterns when compared to prior heat shock. These studies are consistent with previous studies that indicate prior exposure to extreme temperatures and hypoxia can protect neural operation against high temperature stress. They further suggest that the protective mechanism is a time-dependent process best revealed during prolonged exposure to extreme temperatures and is mediated by a neuromodulator such as serotonin.  相似文献   

7.
The content of histamine, serotonin, adrenaline and noradrenaline in the thoracic and lymphatic duct lymph and blood as well as absolute quantity of lymph transported biogenic amines and mediators into the general circulation were studied on 68 dogs during anaphylactic and endotoxin shock (ASh and ESh, respectively). Both ASh and ESh were accompanied by considerable changes in the hemodynamics, lymph circulation, content of biologically active substances in lymph and blood and in their lymph transport to the blood stream. The most profound and early changes in the content of biologically active substances during ASh and ESh were found in the lymph, which shows an important role of the lymphatic system in their resorption and transport from organs and tissues into the general circulation.  相似文献   

8.
Serotonin (5-hydroxytryptamine, 5-HT) is an endogenous signalling molecule capable of altering small intestinal motility. Serotonin is normally present in the intestinal lumen and released by enterochromaffin cells of the mucosal epithelium. We found that intraduodenal infusion of exogenous serotonin causes a dose-dependent myoelectric response in the smooth muscle of the small intestine in the conscious rat. The response consists of repetitive bursts of action potentials (RBAP) that are characterized as short bursts of non-propagative myoelectric spiking. RBAP occur intermittently and only during the first 15 min after intralumenal serotonin infusion. After the initial 15 min period, the frequency of RBAP declines, and the myoelectric pattern shifts to prolonged and continuous spiking, eliminating the interdigestive migrating myoelectric pattern. The effects of intralumenal serotonin are not replicated by parenteral or intraperitoneal infusion nor by intralumenal infusion of 5-hydroxytryptophan or 5-hydroxyindoleacetic acid. The response to intralumenal serotonin was eliminated by several specific 5-HT receptor antagonists. On repeated intralumenal administration of serotonin, the RBAP response decreased demonstrating a decreased sensitivity of the muscle contraction on re-exposure to serotonin. We conclude that intralumenal infusion of serotonin can temporarily initiate specific small intestinal muscle events that are not generated by serotonin from other non-lumenal administration sites. We speculate that an afferent neuro-pathway is necessary for the induction of RBAP, since RBAP are not observed from in vitro muscle preparations.  相似文献   

9.
Hormonal imprinting takes place perinatally at the first encounter between the hormone and its target receptor, causing the finishment of the maturation of receptor-signal transduction system. In the presence of an excess of the target hormone or related molecules faulty imprinting develops with life-long consequences. In earlier experiments single neonatal treatment with minute dose of IL-6 caused also prolonged stimulation of IL-6 production. In the present experiment newborn female and male rats were treated with 20 microg serotonin (hormonal imprinting) and were studied for serotonin content of different cell types in adult age. Serotonin content was measured by flow cytometry and its localization was determined by confocal microscopy. Serotonin content was detected in white blood cells (lymphocytes, monocytes and granulocytes); in lymphocytes, monocytes (macrophages), granulocytes and mast cells of peritoneal fluid and thymic lymphocytes. Serotonin was present in all cell types of control animals studied. Serotonin content extremely elevated in the white blood cells and also increased in the peritoneal cells of neonatally treated female animals. There was no elevation in thymic lymphocytes. The mean values of male animals remained at the control level. The experiments call attention to the life-long effect of the perinatal hormonal imprinting manifested presently in the elevation of serotonin content and point to the gender differences of serotonin imprinting. Considering the role of serotonin in mood and psychiatric diseases, the observations could have some clinical importance.  相似文献   

10.
The effects of serotonin, dopamine and noradrenaline on RNA synthesis, estimated by the incorporation of [3H]orotic acid, were studied on regenerating fragments of planarians. Serotonin was observed to inhibit, whereas dopamine and noradrenaline had no apparent action. These three neurohormones and their antagonists were also tested on planarian cell cultures, using [3H]-uridine as tracer. RNA synthesis, inhibited by serotonin, methiothepine (serotonin antagonist) and fluphenazine (dopamine antagonist), was shown to be restored by dopamine. The effects of serotonin, dopamine and their antagonists, are discussed in relation to the adenylate cyclase system.  相似文献   

11.
Cholinergic drugs can modulate anaphylactic shock and change lymphocyte functions. Plasma proteins modulate effects of muscarinic antagonists during anaphylactic shock. The present investigation was carried out to study the antianaphylactic activity of methacine (antagonist at muscarinic receptors) in combination with neostigmine (anticholinesterase drug). However, it is not known whether plasma proteins-albumin, C-reactive protein (CRP) and immunoglobulin G (IgG) - modify the effects of cholinergic drugs like methacine, serotonin (5-HT) level in the lymphoid organs and quantity of antibody-forming cells (AFC) in the spleen of guinea pigs during experimental anaphylactic shock. It was shown that administration of methacine with neostigmine (40 min and 15 min prior to shock induction, accordingly) at the pathochemical stage revokes shock development. By blocking cholinesterase endogenous acetylcholine is increased and methacine blocks muscarinic receptors and therewith unwanted side effects in the airways (bronchoconstriction) and heart (bradycardia). Administration of the combination of methacine with neostigmine at the immunological stage (guinea pig sensitization) does not affect the course of anaphylactic shock. Administration of methacine with IgG at the pathochemical stage of shock significantly decreases shock intensity, while administration of methacine with CRP or albumin has no influence on the shock. Administration of IgG or CRP (not albumin) at the immunological stage of shock and albumin or IgG (not CRP) at the pathochemical stage leads to reduction of the anaphylactic reaction. Application of methacine with neostigmine or IgG (effective combinations of drugs) results in normalization of antibody response in the spleen and 5-HT level in the lymphoid organs. Administration of methacine with CRP or albumin (ineffective combinations of drugs) leads to increase of antibody response in the spleen and 5-HT level in the lymphoid organs. Administration of hexamethonium or aceclidine aggravated anaphylactic shock reaction. Thus, the combination of methacine with neostigmine can regulate the pathochemical stage of shock and the 5-HT release. At the pathochemical stage of shock IgG increases the antianaphylactic activity of methacine, but albumin and CRP abolish it.  相似文献   

12.
Serotonin (5-hydroxytryptamine) is believed to play a pathogenic role in skin damage and various skin abnormalities; however, its mechanism of action remains unknown. We show here that intradermal injection of serotonin in rats induced a marked reduction in the activities of the glycolytic enzymes, phosphofructokinase (EC 2.7.1.11) and aldolase (EC 4.1.2.13), in both the cytoskeletal and cytosolic fractions from skin. Serotonin also decreased the levels of glucose 1,6-bisphosphate in skin, the powerful regulator of glucose metabolism. These serotonin-induced changes were accompanied by a marked decrease in ATP content in skin. All these pathological changes induced by serotonin were prevented by treatment with two structurally different calmodulin antagonists: thioridazine, an antipsychotic phenothiazine, or clotrimazole, from the group of the antifungal azole derivatives that were recently recognized as calmodulin antagonists. The present results suggest that calmodulin antagonists may be effective drugs in the treatment of skin damage under various pathological conditions and diseases in which serotonin levels are increased.  相似文献   

13.
The investigations have been carried out on 116 guinea pigs divided in three groups: the control (first group), the experimental group with animals after acute anaphylactic shock (second group), the animals after histaminic shock (third group). The animals of the experimental (second) group were sensitized with 25% egg white suspension in 0.9% NaCl applied subcutaneously. The same animals were exposed to the action of the antigen in aerosol (second group). The healthy animals were exposed to the action of 1% solution of dihydrochloride histamine (third group). In acute anaphylactic shock a decrease of histoenzymatic activity of phosphorylase A and branching enzyme in liver parenchyma was observed. It has been concluded that in anaphylactic shock there occurred disturbances in the function of the phosphorylase A--branching enzyme system. In histaminic shock the phosphorylase reaction becomes intensified in numerous liver cells. This is possible because the exogenic histamine may lead to the activation of the enzymatic system under studies.  相似文献   

14.
Long-term hyperserotoninemia induces heart valve disease in rats, and cases of cardiac valvulopathies have been reported in patients using ergolines, possibly through activation of the 5-hydroxytryptamine(2B) (5HT(2B)) receptor. The ergoline terguride (transdihydrolisuride) is a 5HT(2B/2C) receptor antagonist. Using a rat model, we have investigated whether terguride could prevent serotonin-induced changes in general and heart disease specifically. During 4 months, twelve Sprague-Dawley rats were given daily subcutaneous serotonin injections; twelve rats received a combination of serotonin injections and terguride by gavage, whereas ten rats were untreated controls. Using echocardiography, rats with aortic insufficiency were found in all 3 groups, while pulmonary insufficiency was only found in two rats injected with serotonin alone. Animals given serotonin alone had significantly higher heart weights compared to the controls (p=0.029) and rats given terguride (p=0.034). Rats injected with serotonin alone developed macroscopic skin changes at the injection sites, histologically identified as orthokeratosis and acanthosis. Terguride completely prevented these changes (p=0.0001, p=0.0003). Liver weights were higher in the animals given serotonin alone compared to controls (p=0.014) and terguride treated animals (p=0.009). Stomach weights were higher in animals given serotonin alone compared to rats given terguride (p=0.012). In the mesenchymal cell-line MC3T3-E1, terguride almost completely inhibited serotonin-induced proliferation (p<0.01). Serotonin increases heart, liver and stomach weights, possibly through enhanced proliferation. Terguride inhibits these effects. We propose that terguride may have beneficial effects in the treatment of diseases such as carcinoid syndrome, where serotonin plays an important pathogenic role.  相似文献   

15.
The neurotransmitter serotonin (5-HT) plays an important role in a number of behaviors inAplysia californica some of which have been shown to vary with age. We were thus interested in examining the age-dependence of 5-HT inA. californica. Because animals of the same age can have very different weights, and weight alone is reliably known for wild-caught animals, we also examined the variation of 5-HT with weight. Serotonin was measured in the ring and abdominal ganglia combined, in lab-reared animals from 3 to 12 months post-hatch across a wide weight range. Serotonin increased rapidly from 4 to 6 months, and more slowly from 6 to 13 months. Serotonin scaled by soluble ganglion protein increased from 3 to 6–7 months, reached a maximum, and then decreased again. Serotonin, but not scaled 5-HT, increased significantly with weight across the whole weight range. Animals of the same weight, but different ages, had different 5-HT levels, as did young animals of the same age but different weight. Serotonin varied significantly with both age and weight, with the age-dependence being the more significant.  相似文献   

16.
The biochemical mechanisms of serotonergic and adrenergic action on skeletal muscle cyclic nucleotide, glycogen, and amino acid metabolism have been investigated in intact rat epitrochlaris skeletal muscle preparations. Endogenous catecholamine levels in these preparations were 28.6 +/- 2.1 pg/mg of muscle. Release of these catecholamines by tyramine produced a 25% inhibition of alanine and glutamine release. Pretreatment of animals in vivo with 6-hydroxydopamine depleted catecholamine content by 85%. On incubation, preparations from these pretreated animals showed no effect of tyramine on amino acid metabolism. Serotonin (10(-5) M) and epinephrine (10(-5) M) inhibited alanine and glutamine release equally in preparations from 6-hydroxydopamine-pretreated as compared to control rats. Adrenergic antagonists such as dl-propranolol (10(-8)-10(-6) M), oxprenolol (10(-8)-10(-6) M), and practolol (10(-6)-10(-4) M) blocked equally the inhibition of alanine and glutamine release, prevented the stimulations of muscle cAMP levels, phosphosphorylase a formation, and the depletion of muscle glycogen produced by either epinephrine or serotonin. In contrast, serotonergic antagonists such as methysergide (10(-8)-10(-6) M) and cyproheptadine (10(-8)-10(-6) M) blocked the inhibition of alanine and glutamine release, the stimulations of muscle cAMP levels and phosphorylase a formation, and the decreased muscle glycogen content effected by serotonin but not by epinephrine. Incubation of muscles with both epinephrine and serotonin together produced additive stimulation of muscle cAMP levels, but not of the inhibition of alanine and glutamine release. These data indicate that the action of these agonists on skeletal muscle protein and amino acid, glycogen, and cyclic nucleotide metabolism proceeds directly via separate and discrete serotonergic and adrenergic receptor-adenylyl cyclase mechanisms in skeletal muscle.  相似文献   

17.
Serotonin (10-7 M) stimulated cell proliferation in the primary cultures of mouse and human embryonic fibroblasts as well as in mouse L-cells and in monkey kidney cells (MA). The stimulatory effect is completely prevented by pretreatment of cultured cells with serotonin antagonists of tipindole, morphine or cyproheptadine type which do not affect cell proliferation. It is therefore assumed that the stimulatory action of serotonin on these cells is realized via specific serotonin receptors.  相似文献   

18.
Freshwater mussels were analyzed for biogenic amine transmitter substances in gill tissue, suprabranchial nerve and blood. Gill tissue from normal pondwater-acclimated mussels contained significant amounts of monoamine neurotransmitter substances. In comparison with the suprabranchial nerve the gill tissue contained 42% of the dopamine, 7% of the serotonin and 490% of norepinephrine. Exposing the animals to deionized water (salt-depleted) resulted in a loss of transmitter substances from gill tissue, but serotonin reduction was modest. The mussel gill tissue content of serotonin and the precursor tryptophan was regulated at nearly constant levels. Serotonin is an important transmitter substance in mussels and the many functions it controls, including sodium transport regulation, would depend on its continued presence.  相似文献   

19.
Serotonin functions as a neurotransmitter in the central nervous system and takes part in vascular tone, gastrointestinal motility, and blood coagulation at the periphery. New data on a correlation between serotonin level in platelets and cerebrospinal fluid (Audhya et al., 2012) have renewed interest in the hypothesis that considers a platelet as a model of serotoninergic neuron. In this study, using high performance liquid chromatography, we compared the serotonin level in platelets, serum and different brain regions in 6- and 24-month-old rats. It was found that serotonin level decreased from 0.768 to 0.359 μg per 109 cells in platelets and increased in midbrain from 0.260 to 0.439 μg per 1 g of wet weight during the animal aging. The differences between young and old animals in the serotonin level in serum and other brain regions were statistically not significant. Hence, despite the attractiveness of the hypothesis considering the platelet as a neuron model the data on the platelet serotonin transport should be extrapolated on the neuronal transport with caution, especially for the aging process.  相似文献   

20.
The role of the dopaminergic and serotonergic system was studied during the embryonic development of the pond snail Lymnaea stagnalis, with special attention to the effect of dopamine and serotonin as well as their agonists and antagonists on the rotation of the veliger larvae, and to the effect of precursors and inhibitors of the synthetizing enzymes on the duration of the embryonic life. Serotonin, D-lysergic acid diethylamide and N,N-dimethyltryptamine increased at a concentration of 1 microM the rotation by 50%, 90% and 87% respectively, and among them D-Lysergic acid diethylamide was found to be the most potent agonist. Other serotonergic agonists and antagonists enhanced the frequency of the rotation (from 165% to 355%) at higher threshold concentrations in the following rank order: methysergid > tryptamine > 2,5-dimethoxy-4-iodoamphetamine > 5-carboxyamidotryptamine > bromo-lysergic acid diethylamide > 7-methyltryptamine. Application of 1-(2-methoxyphenyl) piperazine decreased the rotation by 76%. The reuptake inhibitor desipramine completely blocked the rotation and killed the embryos. Dopaminergic agonists accelerated the rotation by 62% to 233%, and their effect was ranged as follows: dopamine > apomorphine > m-tyramine approximately equal to p-tyramine. Chlorpromazine at 100 microM concentration killed the embryos. At a concentration of 100 microg/ml, tyrosine, the precursor of DA, slowed down the embryonic development by increasing the duration of the embryonic life from 8 to 10 days. Decarboxylase inhibitors, alpha-methyl-3,4-dihydroxyphenyl-alanine (25 microg/ml) and m-hydroxybenzylhydrazin (5 microg/ml), killed 50% of the embryos, meanwhile the rest hatched ten days later, compared to the control animals. The development was partially blocked by the serotonin precusor L-tryptophane (50 microg/ml). Trytophan hydroxylase blocker, p-chlorphenylalanine (50 microg/ml) resulted in a distortion of the body pattern of the embryos, and prevented the hatching of most (95%) of the animals.  相似文献   

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